Chloroacetyl chloride → 6-(4-Benzyloxyphenyl)-4-propylmorpholin-3-one

HRID 2102348Notes

Reaction equation

HRID 2102348 reaction equation
[OH-].[Na+].[CH2:3]([O:10][C:11]1[CH:16]=[CH:15][C:14]([CH:17]([OH:23])[CH2:18][NH:19][CH2:20][CH2:21][CH3:22])=[CH:13][CH:12]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.Cl[CH2:25][C:26](Cl)=[O:27].[OH-].[K+]>O.ClCCl.C(O)(C)C>[CH2:3]([O:10][C:11]1[CH:12]=[CH:13][C:14]([CH:17]2[CH2:18][N:19]([CH2:20][CH2:21][CH3:22])[C:26](=[O:27])[CH2:25][O:23]2)=[CH:15][CH:16]=1)[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1

Participants

8

Reactant 4

HCID 6577Chloroacetyl chlorideHCID 14797Potassium HydroxideHCID 14798Sodium HydroxideHCID 574406901-(4-Benzyloxyphenyl)-2-propylaminoethanol

Product 1

HCID 574406916-(4-Benzyloxyphenyl)-4-propylmorpholin-3-oneYield 67%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 3776IsopropanolSolventHCID 6344DichloromethaneSolvent

Procedure

Sodium hydroxide (22.5 g, 0.56 mol) in water (100 ml) was added to the amine from example 26 (26.0 g, 0.09 mol) in dichloromethane (400 ml) and the solution vigorously stirred at room temperature. Chloroacetylchloride (8.6 ml, 0.11 mol) was then added and the reaction mixture stirred for a further 60 minutes. The layers were separated and the aqueous layer re-extracted with dichloromethane (200 ml). The organic extracts were combined, dried over anhydrous magnesium sulphate, filtered and concentrated in vacuo to give a colourless oil. Potassium hydroxide (15.0 g, 0.27 mol), isopropyl alcohol (400 ml) and the colourless oil residue were stirred together as an opaque solution with water (30 ml) for 2 hours. The reaction mixture was concentrated in vacuo and the yellow residue dissolved in ethyl acetate (200 ml). This was partitioned with water (200 ml) then brine (200 ml). The organic fraction was dried over anhydrous magnesium sulphate, filtered and concentrated in vacuo to give the title compound as a white solid (19.9 g, 0.06 mol, 67%). 1H NMR (CDCl3, 400 MHz) δ: 0.95 (t 3H), 1.62 (m, 2H), 3.34 (m, 2H), 3.51 (m, 2H), 4.32 (d, 1H), 4.41 (d, 1H), 4.72 (dd, 1H), 5.04 (s, 2H), 6.98 (d, 2H), 7.31-7.43 (m, 7H). LRMS: m/z 326 (M-H+).

Workup

  1. stirringthe reaction mixture stirred for a further 60 minutes
  2. customThe layers were separated
  3. extractionthe aqueous layer re-extracted with dichloromethane (200 ml)
  4. dry with materialdried over anhydrous magnesium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto give a colourless oil
  8. concentrationThe reaction mixture was concentrated in vacuo
  9. dissolutionthe yellow residue dissolved in ethyl acetate (200 ml)
  10. customThis was partitioned with water (200 ml)
  11. dry with materialThe organic fraction was dried over anhydrous magnesium sulphate
  12. filtrationfiltered
  13. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-295e9b1dac8344a1932cf017c7c11d2e
Source dataset
uspto-grants-2009_08
Patent number
US07576081B2

Reaction notes

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